D2.346 - Assessment of the safety of allogenic natural killer cells in the treatment of metastatic colon cancer
Background
Natural killer (NK) cells are innate immune cells that play an important role as first-line defenders in anti-tumor response. Their anti-tumor functions include secretion of lytic granules, expression of death receptors and production of cytokines. The innate tumor-killing ability of NK cells makes them attractive candidates for tumor control. In the present study the safety of allogenic NK infusion for the treatment of metastatic colon cancer was assessed.
Method
16 patients with metastatic colon cancer participated in the trial. CD3–CD56+ NK cells from healthy volunteers, isolated by immunomagnetic separation were cultured in RPMI-1640 medium with 10.0% FBS, 10 ng/ml IL-2 and 10 ng/ml IL-15 for 12–14 days, adding fresh medium and cytokines every 2-3 days for cell biomass accumulation. NK were identified as CD45+CD3–CD56+ cells expressing cytolytic proteins Granzyme B, Perforin and Granulysin. Selection of donor and recipient was based on HLA typing of patients (HLA-C2, HLA-C1, HLABw4) and KIR receptor immunophenotyping (KIR2DL1, KIR2DL2/DL3, KIR3DL1) of donors (KIR-HLA mismatch). NK cells were infused in an average dose of 1x106 per kg of body weight intravenously over 60 minutes.
Results
General adverse reactions such as increased or decreased blood pressure, heart rate were not registered. Three patients out of 16 had fever the next day after therapy. No allergic reactions were detected. A thorough assessment of the parameters of blood, urine and a biochemical blood tests was performed. There were no significant changes that indicate hepatotoxic, nephrotoxic and hematotoxic effects of NK application. One-year survival of patients was 93.3%.
Conclusion
Allogenic Natural Killer Cells in the treatment of metastatic colon cancer were not associated with allergic reactions or other adverse effects except fever which was registered in 3 out of 16 patients. Application of NK in the treatment of metastatic colon cancer appears safe and well tolerated.
